The delivery of drugs through the skin provides many advantages; primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences--e.g., gastrointestinal irritation and the like--are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug.
Skin is a structurally complex, relatively thick membrane. Molecules moving from the environment into and through intact skin must first penetrate the stratum corneum and any material on its surface. They must then penetrate the viable epidermis, the papillary dermis, and the capillary walls into the blood stream or lymph channels. To be so absorbed, molecules must overcome a different resistance to penetration in each type of tissue. Transport across the skin membrane is thus a complex phenomenon. However, it is the cells of the stratum corneum which present the primary barrier to absorption of topical compositions or transdermally administered drugs. The stratum corneum is a thin layer of dense, highly keratinized cells approximately 10-15 microns thick over most of the body. It is believed to be the high degree of keratinization within these cells as well as their dense packing which creates in most cases a substantially impermeable barrier to drug penetration.
In order to increase skin permeability, and in particular to increase the permeability of the stratum corneum (i.e., so as to achieve enhanced penetration, through the skin, of the drug to be administered transdermally), the skin may be pretreated with a penetration enhancing agent (or "permeation enhancer", as sometimes referred to herein) prior to application of a drug. Alternatively, and preferably, a drug and a permeation enhancer are concurrently delivered.
The present invention is directed to a novel composition for enhancing the penetration of pharmacologically active agents through skin, the composition in a preferred embodiment comprising a combination of diethylene glycol monoethyl ether (available under the trademark Transcutol from Gattefosse; sometimes referred to herein as "TC") with at least one long-chain ester, e.g., of lauric acid, including glycerol monolaurate ("GML"), propylene glycol monolaurate ("PGML"), propylene glycol dilaurate ("PGDL"), methyl laurate ("ML"), ethyl laurate ("EL"), or the like. Surprisingly, this combination has been found by the inventor herein to be more effective in enhancing the penetration of pharmacologically active agents through skin than either Transcutol or a lauric acid ester alone. The novel enhancer composition is particularly effective in conjunction with the transdermal administration of steroid drugs.
While there are a number of patents and publications available which relate to the transdermal administration of steroid drugs, to the use of Transcutol as a skin permeation enhancer, and to combination-type enhancer compositions, applicant is unaware of any art which relates to the "combination" enhancer composition disclosed and claimed herein or to the use of such an enhancer composition with a steroid drug.